Despite the advances in management of end stage chronic renal disease, anemia persists as an almost constant complication seen in these patients. It is believed that the common denominator underlying this anemia is an impaired erythpoietin production by a diseased kidney but it appears that there are many additional factors that determine the degree of anemia in a given patient. It is our objective to determine and define these factors in order to develop a more rational therapeutical approach to the anemia of chronic renal disease. We will study the alterations in oxygen sensing and erythropoietin production by a diseased kidney. We would like to characteize the number and responsiveness of erythroid stem cells in patients with anemia of chronic renal disease, and study the role of uremic toxins and cell-cell interactions in the genesis of this anemia. We would like to define better the effectiveness of dialysis and define its mechanisms of action. Our methods and procedures will include both the study of patients with end stage renal disease and the development of an animal model of chronic uremia. Specific methods will indluce determination of erythropoietin by biological and immunological methods, and bone marrow cultures to determine the responsiveness of erythroid precursors in vitro. There are currently approximately 40,000 patients on chronic dialysis in this country. Although anemia is usually managed with androgens and blood transfusions, it significantly affects the quality of life of these patients. A better understanding of the pathogenesis of this anemia could improve its management and provide the necessary groundwork for the future use of erythropoietin in clinical trials. Animals involved: Rats and mice.